Introduction. In CV-1 cells, shuttling from cytoplasm to nucleus of the nuclear thyroid hormone receptor-01 (TB/31, TR) is shown in this report to be regulated by extracellular thyroid hormone at a hormone receptor on cell surface integrin av3. Methods. The receptor was introduced into cells as a GFP-TR1 chimera and intracellular movement of the receptor was monitored by confocal microscopy of cells treated with L-thyroxine (T 4). Results and Discussion. TR-GFP translocation in the presence ofT 4 requires activation of extracellular-regulated protein kinases 1/2 (ERK1/2). Inhibition of Tj-binding to av/33 with anti-av/33 or Arg-Gly-Asp (RGD) peptide blocks TfStimulated GFP-TR nuclear translocation, as do the hormone-binding inhibitor tetraiodothyroacetic acid (tet-rac) and the ERK1/2 inhibitor, PD98059. TR1 is an ERK1/2 substrate. Conclusions. Via a nongenomic mechanism initiated at plasma membrane integrin v3, T 2a-activated ERK1/2 and TR1 move transiently in an immunoprecipitable comphx to the nuclei of T 2a-treated cells.
ASJC Scopus subject areas